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Neo-antigen tumor vaccination depends on CD4-licensing conveyed by adeno-associated virus like particles

Personalized treatment has become a realistic option for tumor patients, accelerated by significantly reduced sequencing costs of tumor genomes and advances in vaccine formulations. The druggability of cancer neo-antigens caused by individual mutations is centered in this effort. We here use an aden...

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Main Authors: Neukirch, Lasse (Author) , Uhrig-Schmidt, Silke (Author) , Werthern, Katharina von (Author) , Tuch, Alexandra (Author) , Kraske, Joscha (Author) , Lyu, Yanhong (Author) , Lenoir, Benedicte (Author) , Eichmüller, Stefan B. (Author) , Meyer, Marten (Author) , Zörnig, Inka (Author) , Jäger, Dirk (Author) , Schmidt, Patrick (Author)
Format: Article (Journal)
Language:English
Published: 1 October 2025
In: Molecular therapy
Year: 2025, Volume: 33, Issue: 10, Pages: 5003-5016
ISSN:1525-0024
DOI:10.1016/j.ymthe.2025.07.014
Online Access:Verlag, kostenfrei, Volltext: https://doi.org/10.1016/j.ymthe.2025.07.014
Verlag, kostenfrei, Volltext: https://www.sciencedirect.com/science/article/pii/S1525001625005490
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Author Notes:Lasse Neukirch, Silke Uhrig-Schmidt, Katharina von Werthern, Alexandra Tuch, Joscha A. Kraske, Yanhong Lyu, Benedicte Lenoir, Stefan B. Eichmüller, Marten Meyer, Inka Zörnig, Dirk Jäger, and Patrick Schmidt
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Summary:Personalized treatment has become a realistic option for tumor patients, accelerated by significantly reduced sequencing costs of tumor genomes and advances in vaccine formulations. The druggability of cancer neo-antigens caused by individual mutations is centered in this effort. We here use an adeno-associated virus (AAV)-based virus-like particle (VLP) platform to compose a neo-antigen-specific protein vaccine that is effective in a murine prevention and treatment setting. Furthermore, we show that CD4+ T cell responses that are provided by the AAV capsid are crucial for effective murine melanoma treatment. To uncover the optimal composition of a peptide vaccine we de-linked major histocompatibility complex (MHC) class II helper peptides from the capsid and formulated an efficient neo-antigen-specific vaccine, which showed the independence of CD4+ T cell response from tumor sequences. The findings are supported by clinical data of neo-antigen-vaccinated tumor patients. Our results punctuate on the significance of MHC class II epitopes for CD8+ T cell responses and suggest a future use of AAVLPs as neo-epitope vaccines in personalized cancer treatments.
Item Description:Online verfügbar: 16. Juli 2025, Artikelversion: 1. Oktober 2025
Gesehen am 23.03.2026
Physical Description:Online Resource
ISSN:1525-0024
DOI:10.1016/j.ymthe.2025.07.014

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